The Herpes Group of viruses includes many viruses which are pathogenic in humans, such as Herpes Simplex Virus (HSV), Varicella Zoster Virus (VZV), Cytomegalovirus (CMV), and Epstein-Barr Virus (EBV). In this group, B-capsids are essential intermediate structures in virion replication and are formed during the assembly of viral capsids in cell nuclei. One of the more abundant protein components of B capsids, the assembly protein, undergoes proteolytic pressing at its C-terminus and is packaged in mature, infectious virions only in its shortened, mature form (Gibson W. and Roizman, B. 1972. J. Virology 10:1044-1052).
For HSV, the assembly protein is designated ICP35. The protease which acts on the assembly protein is encoded in the same open reading frame as the ICP35 assembly protein, designated the U.sub.L 26 gene (Liu, F. and Roizman, B. 1992 Proc. Natl. Acad. Sci. USA 89:2076-2080). The catalytic domain of the protease is contained within the first 247 amino acids of a 635 amino-acid protein and is apparently released from the precursor through cleavage by the HSV protease itself (Weinheimer, S. P. et al., 1993 J. Virology 67:5813-5822; Welch, A. R. et al., 1991, Proc. Natl. Acad. Sci. USA 88: 10792-10796; Deckman, I. C. et al., 1992, J. Virol. 66: 7362-7367).
Protease activity appears to be essential for viral replication within the entire group of herpes viruses. Thus, it would be desirable to characterize the herpes group proteases as potential antiviral targets. However, the herpes viral proteases, in the form of fusion proteins, have only been partially purified. (Dilanni, C. L. et al., 1993, J. Biolog. Chem. 268:25449-25454; and Weinheimer, S. P. et al., supra). Other herpes proteases (cmv) have been purified and described (see, e.g. WO 93/01291, published Jan. 21, 1993, Applicant: The Johns Hopkins University).